Papillon-Lefevre syndrome Clinical study PAPILLON-LEFEVRE SYNDROME (PLS) A. A. Kansky, M. Potočnik and A. Kansky ABSTRACT Background. The syndrome was first described by Papillon and Lefevre in 1924, it is characterized by palmoplantar hyperkeratosis and severe periodontal breakdown, resulting in early loss of teeth. Objective. The authors were engaged in obtaining data on Papillon-Lefevre cases in the population of Slovenia. Methods. Clinical records were studied and patients' families were investigated at their homes. Among the 2 million Slovenian population 13 persons were detected in 7 families. Consanguinity could not be proven. 11 affected persons were monitored by the investigators. Results. The patients who cooperated in the study, showed in most cases psoriasis-like skin lesion and palmoplantar hyperkeratosis. A severe periodontitis appeared soon after the teeth eruption. Some of them were treated with antibiotics and retinoids, nonetheless they lost all the teeth up to the end of puberty. Conclusion. The genetic defect remains unknown, The therapy is symptomatic: antibiotics and good dental cleaning are important. Retinoids influence primarily the skin lesions. Cooperation between dermatologist and stomatologist is needed and an early treatment is indicated. KEY WORDS Papillon-Lefevre syndrome, hereditary hyperkeratosis with periodontosis, patients, Slovenia INTRODUCTION The combination of a transgredient palmoplantar hyperkeratosis which is usually mild with a severe periodontal breakdown, resulting in early loss of both, the deciduous and permanent teeth was first described by Papillon and Lefevre in 1924 (1) . Until now about 200 cases of the Papillon-Lefevre syndrome (PLS) have been described. During the 1994-95 period, 17 cases were reported (2,3,4,5,6,7,8). However, exact numbers cannot be given while some cases 60 are mentioned two times or more, and certain cases are not reported. Though most case reports deal with Caucasians there are also PLS reports from Mongoloid and Negroid races. It is interesting to note that in Slovenia with its 2 million inhabitants 11 PLS patients were diagnosed (9). The syndrome may be supposed to be more frequent than believed, since dentists may overlook the mild palmar and plantar hyperkeratosis and dermatologists may not acta dermatovenerologica A .P.A. Vol 6, 97, No 2 + + I II III I Fam. A + II I III II Fam. C III w I Fam. B II Fam. D I II + III IV I Fam. F I II II III Fam. E Fam. G Fig. l. Pedigrees of 7 families in Slovenia in which 13 patients affected with Papillon-Lefevre syndrome are presented acta dennatovenerologica A.P.A. Vol 6, 97, No 2 61 Papillon-Lefevre syndrome Fig. 2. The 17-year-old patient KB. (family G). Reddened and mildly hyperkeratotic palms, hyperkeratosis is particularly expressed on her soles. be aware of the unique loss of teeth. An autosomal recessive inheritance is assumed. The genetic defect remains unknown. CLINICAL SYMPTOMS Specific criteria for diagnosing PLS are: l. periodontitis and alveolar pyorrhoea 2. premature loss of all deciduous and permanent teeth 3. palmar and plantar hyperkeratosis 4. sharply delineated psoriasis-like skin lesions on other parts of the body Fig. 3. The patient is toothless, her alveolar ridge atrophic. 5. autosomal recessive inheritance 6. facultative symptoms are increased susceptibility to infections and asymptomatic intracranial calcifications (10). The most consistent symptom is the characteristic loss of all teeth. After the normally shaped deciduous teeth erupt, a severe inflammation of the gingiva appears, with periodontitis and pocket formation leading to a complete loss of teeth by the age of 4 to 5 years. The permanent teeth appear at normal tirne and are as a rule !ost in the same way. The periodontal breakdown is usually a consequence of an inflammatory destruction (periodontitis) while a Fig. 4. Panoramic x-ray of the patient KB. at the age of 17 years. She is edentulous, her alveolar ridges are markedly atrophic. 62 acta dermatovenerologica A.P.A. Vol 6, 97, No 2 Papillon-Lefevre syndrome poor oral hygiene and the subsequent accumulation of dental bacterial plaque are contributing factors. Periodontal breakdown in a child or adolescent can be slowned down by maintaining good oral hygiene. The exact mechanisms causing this condition are not known, it seems however that an inborn deficiency of the immune system is an important factor (11). Cutaneous symptoms are characterized by palmar and plantar hyperkeratosis, which is normally accompanied by a moderate hyperhidrosis. Hyper- keratosis often extends to dorsal aspects of the hands and feet (transgression) as well as to the region of the Achilles tendon. Additionally sharply delineated psoriasis-like plaques may be present on elbows, knees, dorsal aspects of the metacarpo- phalangeal joints, but also elsewhere (12). The red colored plaques are covered by a hyperkeratotic stratum corneum or parakeratotic scales. The hair and nails are usually normal, but sparse hair was noted (13). X-rays of the maxilla and the mandible show severe atrophy of the alveo!ar bone. The main reason is the early loss of teeth, which prevents normal jaw development. Further reason for atrophy are inflammation that incites osteolytic processes in the bone and the use of dentures. Laboratory tests show decreased neutrophil phago- cytosis (14). Impaired reactivity to T- and B- cell mitogens (15) with only minimal changes in monocyte function (16) might account for prominent gingival and cutaneous infections. Non-infective mechanisms of disruption of gingival fibroblast and cementoblast function have also been considered (17). Microbiological findings show a close association between Actinobacillus (A) actinomycetemcomitans and the periodontal disease associated with the syndrome. A actinomycetemcomitans by itself is not sufficient for the expression of periodontal disease. Other factors, some of which must be genetic, are necessary for lesion development (18). Histopatho- logica! changes are non-specific but show hyperkeratosis with irregular parakeratosis and a moderate perivascu- lar infiltrate. Electron microscopic findings of skin lesions include lipid-like vacuoles in the corneocytes and granulocytes, reduction in tonofillaments and irregular keratohyalin granules. These changes improve during retinoid therapy (19). TREATMENT: Dental cleaning and antibiotics are still the standard therapy. Etretinate (20), isotretinion (21) and acitretin acta dermatovenerologica A.P.A. Vol 6, 97, No 2 (19) have all been successful in improving the cutaneous lesion, lessening gingival inflammation and in severa! cases, saving the teeth. Recently proposed treatment involving antibiotic coverage (amoxicillin plus clavulanic acid, or ofloxacin), extraction of primary dentition and a period of edentulism has been shown to be effective in maintaining the permanent dentition (22,23). Since treatment should begin prior to eruption of the permanent dentition, early recognition of PLS is critical. Any young patient who exhibits palmar hyperkeratosis should be examined carefully for periodontal breakdown. PLS CASES IN SLOVENIA In Slovenia (about 2 million inhabitants) we found 13 cases in 7 PLS families (24, 25), which is a much higher rate as reported in the literature (1 -3 cases per million). No relationship among the families could be established. Ali patients except one are from Eastem Slovenia. Except for